Cancer Stem Cells

Sharmila Bapat, PHD, is a group leader of a small research group at the National Centre for Cell Science at India's University of Pune. She is an author of the first report on the isolation and identification of stem cells in ovarian cancer. Dr. Bapat organizes workshops on topics such as cell line establishment, immortalization of cultured cells, and stem cell protocols. She is also on the board of editors of the recently launched Journal of Ovarian Research.

• Contributors xiPreface xiii1 Cancer Stem Cells: Similarities and Variations in the Theme of Normal Stem Cells 1Sharmila Bapat, Anne Collins, Michael Dean, Kenneth Nephew, and Suraiya Rasheed1.1 Introduction 11.2 Stem Cells in the Life of an Organism 21.2.1 Stem Cells in Early Development and Fetal Life 31.2.2 Stem Cells in the Adult Organism 41.3 Cancer Stem Cells 71.3.1 Activation of Stem Cells and Cancer 71.3.2 Isolation and Identification of Cancer Stem Cells 101.3.3 De Novo Generation of a New Organ (Tumor) by Transformed Stem Cells 121.4 Self-Renewal and Differentiation in CSCs 131.5 CSC Plasticity as Regulated by Intrinsic and Extrinsic Stem Cell Factors 141.5.1 Stem Cell Intrinsic Factors: Genetic and Epigenetic Effects 141.5.2 Stem Cell Extrinsic Effects: Niche Effects and Microenvironmental Signaling 161.6 Conclusions and Future Perspectives 18References 202 Leukemic Stem Cells 27Sharmila Bapat2.1 Introduction 272.2 Dysregulation of Hematopoiesis in Leukemia 282.2.1 Normal Hematopoietic Stem Cell Hierarchies 282.2.2 Understanding Aberrant Hierarchies in Leukemia 302.2.3 Types of Leukemia 312.3 Identification and isolation of Cancer-Initiating Cells in Leukemia 352.4 Molecular Regulation of Aberrant Hierarchies 362.4.1 Signaling Pathways Deregulated in Leukemia 372.4.2 Self-Renewal of Normal and Leukemic Stem Cells 392.4.3 Epigenetic Effects 402.4.4 MicroRNA in Leukemia Development 422.5 Conclusions and Future Perspectives 44References 453 Isolation and Characterization of Breast and Brain Cancer Stem Cells 57Meera Saxena and Annapoorni Rangarajan3.1 Introduction 573.2 Breast Cancer Stem Cells 583.2.1 Mammary Gland Architecture and Cell Types 583.2.2 Breast Cancer 593.2.3 Identification of Breast Cancer Stem Cells 593.2.4 Putative Breast Cancer Stem Cells that Exhibit the CD44+ CD24-/low Lin- Marker Profile 613.2.5 ESA+ Subpopulation of CD24-low Lin- Cells Enriched by Tumorigenicity 613.2.6 Tumorigenic Breast Cells Displaying Properties of Stem Cells 613.2.7 In Vitro Propagation of Breast Cancer Stem Cells as Mammospheres 623.3 Brain Cancer Stem Cells 643.3.1 Brain Architecture and Cell Types 643.3.2 Brain Cancers 653.3.3 Brain Stem Cells 663.3.4 Brain Cancer Stem Cells 663.3.5 Brain Cancer–Derived Cells that Generate Tumor Spheres 673.4 Conclusions and Future Perspectives 69References 704 Cancer Stem Cell Side Populations 73Danuta Balicki and Raymond Beaulieu4.1 Introduction 734.2 Stem Cell Side Populations 754.3 Side Populations in Normal Tissue 784.4 Side Populations in Tumors 794.5 Overcoming Side Population Limitations 804.6 Conclusions and Future Perspectives 81References 825 Evidence for Cancer Stem Cells in Retinoblastoma 87Gail M. Seigel5.1 Introduction 875.2 Elusive Origins of Retinoblastoma 875.3 Sources of Retinoblastoma Cells for Study 885.4 Precedent for Cancer Stem Cells 885.5 Side Populations in Retinoblastoma 895.6 Immunoreactivity to Stem Cell Markers in Retinoblastoma 895.7 Conclusions and Future Perspectives 91References 926 Ovarian Stem Cell Biology and the Emergence of Ovarian Cancer Stem Cells 95Anjali Kusumbe and Sharmila Bapat6.1 Introduction 956.2 Overview of the Human Ovary 956.2.1 Histological Landmarks 956.2.2 Ovarian Development: The Story Before Birth 966.2.3 The Mammalian Oogenesis Dogma 986.3 Stem/Progenitor Cells in the Adult Mammalian Ovary 986.3.1 Historical Perspective 986.3.2 The Oogenesis Dogma Revisited 996.4 Is Ovarian Cancer a Stem Cell Disease? 1046.4.1 Putative Role of Stem/Progenitor Cells in Ovarian Cancer 1046.4.2 Tumor as an Aberrant Organ Initiated by Cancer Stem Cells 1056.4.3 Ovarian Cancer Stem Cells Isolated as a Side Population 1066.4.4 New Challenge: Targeting Ovarian Cancer Stem Cells 106References 1077 Prostate Cancer Stem Cells 111Stefanie Hager, Norman J. Maitland, and Anne Collins7.1 Introduction 1117.2 Human Prostate Biology Gland Architecture, and Pathological Alterations 1117.3 Prostate Epithelial Stem Cells 1137.3.1 Evidence for Prostate Epithelial Stem Cells 1137.3.2 Isolation of Human Prostate Epithelial Stem Cells and Demonstration of Their Stem Cell Character 1167.3.3 Epithelial Stem Cells in the Murine Prostate 1187.3.4 Other Markers of Prostate Epithelial Stem Cells 1197.4 Prostate Cancer Stem Cells 1207.4.1 Role of Stem Cells in Prostate Cancer 1207.4.2 Prospective Isolation of Prostate Cancer Stem Cells from Human Tissue Samples 1227.4.3 Role of the Stem Cell Niche in Prostate Cancer 1247.4.4 Putative Markers of Prostate Cancer Stem Cells 1247.5 Stem Cell Tracking in the Prostate 1257.6 Conclusions and Future Perspectives 127References 1278 Molecular Signatures of Highly Malignant Melanoma Stem Cells 135Suraiya Rasheed8.1 General Properties of Human Melanomas 1358.2 Characteristics of Stem Cell–Derived Melanomas 1368.3 The Cat Model System for Stem Cell Melanomas 1378.3.1 Biological Characteristics of Highly Malignant Stem Cell Melanomas 1388.3.2 Trans-differentiation of the Malignant Cat Melanoma into Neuronal Cells 1398.3.3 Proteins Associated with Neuronal Cell Differentiation 1408.3.4 Cell Cycle Dysregulation and Antitumorigenic Effects During Cell Differentiation 1448.3.5 Molecular Signatures of Self Renewal and Long-Term Proliferation of Tumor Cells 1458.3.6 Proteins Involved in Tumorigenesis and Metastasis 1478.3.7 Expression of Germline and Embryonic Proteins in Cat Melanomas 1498.3.8 Naturally Occurring Protein–Protein Interaction Complexes in Melanomas 1498.3.9 Networks of Protein Interaction Pathways 1528.4 Challenges of Research in Cancer Stem Cellsand Therapeutics 1528.5 Conclusions and Future Perspectives 154References 1569 Invasion Program of Normal and Cancer Stem Cells 167David Olmeda, Gema Moreno-Bueno, David Sarrió, José Palacios, and Amparo Cano9.1 Introduction 1679.2 Basics of Tumor Progression: Invasion and Metastasis 1689.3 Epithelial-to-Mesenchymal Transition in Development and Its Relation to The Invasive Process 1699.4 Regulation of EMT: From Signals to Molecular Pathways 1729.5 EMT and Cancer Stem Cells 1769.6 Can Stem Cell Properties Be Extensive to Invasive Tumor Cells? 1779.7 Is There a Unique EMT Program Linked to Invasion? 1789.8 Evidence of EMT in Human Clinical Tumors 1809.9 Expression of Mesenchymal Markers and Cadherin Switching in Carcinomas 1819.10 Expression of EMT Inducers in Human Tumors 1839.11 Occurrence of EMT in a Specific Subset of Breast Carcinomas 1859.12 Conclusions and Future Perspectives 186 References 18710 Epigenetics in Cancer Stem Cell Development 197Kenneth Nephew, Curt Balch, Tim H.-M. Huang, Zhang Shu, Michael Chan, and Pearlly Yan10.1 Introduction 19710.2 Characterization of Candidate Cancer Stem Cells 19810.3 Possible Origins of Cancer Stem Cells 19810.4 Epigenetics in Normal Development 19910.5 Epigenetic Regulation of the Cancer Stem Cell Phenotype 20010.6 Contributions of Epigenetics to Drug Resistance in Cancer Stem Cells 20410.7 Genome-Wide Interrogation of Epigenetic Modifications in Cancer Stem Cells 20610.8 Epigenetic Therapies Against Poorly Differentiated Cancer Cells 20710.9 Conclusions and Future Perspectives 208References 20911 Cancer Stem Cells and New Therapeutic Approaches 217Michael Dean11.1 Cancer Stem Cells 21711.2 Activation of Stem Cells and Cancer 21811.2.1 Initiation and Promotion Revised 21911.2.2 Stem Cell Activation and Specific Cancers 22111.3 Major Cancers and Risk Factors 22311.3.1 Liver Cancer 22311.3.2 Lung Cancer 22411.3.3 Gastric Cancer 22411.3.4 Pancreatic Cancer 22411.3.5 Cervical Cancer 22511.4 Treatment Implications 22511.5 Future Perspectives 22711.6 Conclusions 228References 24312 Immunobiology of Cancer Stem Cells 233Shubhada V. Chiplunkar12.1 Cancer Stem Cells 23312.2 Cancer Stem Cells and Lymphocytes 23412.3 Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells 236References 238Index 243

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